The effect of learning a one trial passive avoidance response and of psychotropic drugs on the turnover of acetylcholine (ACh) in discrete regions of rat brain will be studied. At various times after training in a passive avoidance paradigm, deuterated choline will be administered to rats and the turnover of ACh in various brain regions implicated in this behavior will be studied. The regions to be studied are hippocampus, striatum, and frontal cortex. Specificity will be ascertained by measuring the turnover in the posterior cortex, a region not implicated in this behavior. Some psychotropic drugs (amphetamine, haloperidol and THC) will be studied for their effects on ACh turnover in the hippocampus, striatum, hypothalamus, olfactory tubercle, frontal and posterior cortex. Where treatments (behavioral or drug) are seen to have an effect on ACh turnover, the effect of the same treatments on the levels and labelling of ACh in synaptosomes isolated from specific regions will be determined. Also, the effects of these treatments on the availability of precursors for the synthesis ACh will be determined. In these experiments, following treatment of rat, brain slices or synaptosomes will be prepared from the specific regions and the high affinity uptake and acetylation of choline and flux of labelled pyruvate and synthesis of ACh will be determined. Similarly, the proportion of pyruvate dehydrogenase in the active form will be determined following treatment. Should the results of these studies indicate, the effects of striatal lesions on behavior and turnover of hippocampal ACh will be studied. To elucidate further the role of cholinergic systems in learning and memory, the effect of an appetitive approach response on ACh turnover in discrete brain regions will be determined. The effects of cholinergic drugs on both learning and turnover of ACh will be studied in the hippocampus and striatum. Experiments to evaluate the utility of cholinergic false transmitters as probes to study cholinergic mechanisms in learning and memory will be performed. This work should show the role of the central cholinergic nervous system in behavior and a mechanism and site of action of some psychotropic drugs.